Short-term lumbar disc and lumbar stability changes of one-hole split endoscope technique treatment of spinal stenosis.

OBJECTIVE: Investigating the early biomechanical effects of the one-hole split endoscope (OSE) technique on lumbar spine after decompression surgery. METHODS: A retrospective analysis was conducted on 66 patients with lumbar spinal stenosis (LSS) who underwent OSE technique surgery at the affiliated hospital of Binzhou Medical University from September 2021 to September 2022. The patients had complete postoperative follow-up records. The mean age was (51.73 ± 12.42) years, including 33 males and 33 females. The preoperative and postoperative imaging data were analyzed, including disc height (DH), foraminal height (FH), lumbar lordosis angle (LLA), changes in disc angle, anterior-posterior translation distance, and lumbar intervertebral disc Pfirrmann grading. The visual analogue scale (VAS) was applied to evaluate the severity of preoperative, postoperative day 1, postoperative 3 months, and final follow-up for back and leg pain. The Oswestry Disability Index (ODI) was applied to assess the functionality at all the listed time points. The modified MacNab criteria were applied to evaluate the clinical efficacy at the final follow-up. RESULTS: In 66 patients, there were statistically significant differences (p < 0.05) in DH and FH at the affected segments compared to preoperative values, whereas no significant differences (p > 0.05) were found in DH and FH at the adjacent upper segments compared to preoperative values. There was no statistically significant difference in the LLA compared to preoperative values (p > 0.05). Both the affected segments and adjacent upper segments showed statistically significant differences in Pfirrmann grading compared to preoperative values (p < 0.05). There were no statistically significant differences in the changes in disc angle or anterior-posterior translation distance in the affected or adjacent segments compared to preoperative values (p > 0.05). The VAS scores for back and leg pain, as well as the ODI, significantly improved at all postoperative time points compared to preoperative values. Among the comparisons at different time points, the differences were statistically significant (p < 0.05). The clinical efficacy was evaluated at the final follow-up using the modified MacNab criteria, with 51 cases rated as excellent, 8 cases as good, and 7 cases as fair, resulting in an excellent-good rate of 89.39%. CONCLUSIONS: The OSE technique, as a surgical option for decompression in the treatment of LSS, has no significant impact on lumbar spine stability in the early postoperative period. However, it does have some effects on the lumbar intervertebral discs, which may lead to a certain degree of degeneration.

Pyroptotic T cell-derived active IL-16 has a driving function in ovarian endometriosis development.

Endometriosis, affecting 6%-10% of women, often leads to pain and infertility and its underlying inflammatory mechanisms are poorly understood. We established endometriosis models in wild-type and IL16KO mice, revealing the driver function of IL-16 in initiating endometriosis-related inflammation. Using an in vitro system, we confirmed iron overload-induced GSDME-mediated pyroptosis as a key trigger for IL-16 activation and release. In addition, our research led to the development of Z30702029, a compound inhibiting GSDME-NTD-mediated pyroptosis, which shows promise as a therapeutic intervention for endometriosis. Importantly, our findings extend beyond endometriosis, highlighting GSDME-mediated pyroptosis as a broader pathway for IL-16 release and offering insights into potential treatments for various inflammatory conditions.

Uptake, Translocation, and Fate of Carcinogenic Aristolochic Acid in Typical Vegetables in Soil-Plant Systems.

When Aristolochia plants wilt and decay, aristolochic acids (AAs) are released into the soil, causing soil contamination. It has been demonstrated that aristolochic acid can be accumulated and enriched in crops through plant uptake. However, there is a lack of systematic studies on the migration and accumulation of AAs in a realistic simulated soil environment. In this study, Aristolochia herbal extracts were mixed with soil for growing three typical vegetables: lettuce, celery, and tomato. The contents of AAs in the above-mentioned plants were determined by an established highly sensitive LC-MS/MS method to study the migration and accumulation of AAs. We found that AAs in the soil can be transferred and accumulated in plants. AAs first entered the roots, which were more likely to accumulate AAs, and partially entered the above-ground parts. This further confirms that AAs can enter the food chain through plants and can have serious effects on human health. It was also shown that plants with vigorous growth and a large size absorbed AAs from the soil at a faster rate. The more AAs present in the soil, the more they accumulated in the plant.

Estrogen receptor beta promotes endometriosis progression by upregulating CD47 expression in ectopic endometrial stromal cells.

Endometriosis is a common estrogen-dependent gynecological disorder that is characterized by endometrial-like tissue being found at extrauterine sites. Aberrant expression and activation of estrogen receptor beta (ERß) in ectopic endometrium are involved in endometriosis development. Here, we used primary tissues and cells from endometriosis patients to investigate the molecular mechanisms involved in ERß's contribution to endometriosis progression. Through RNA-seq, quantitative PCR, and immunohistochemistry analysis, we found that ERß expression is related to the severity of endometriosis; specifically, the ratio of ESR2/ESR1 in ectopic tissues was positively correlated with the severity of endometriosis, which suggests that ERß has a predominant role in endometriosis progression. Furthermore, we found that ERß could bind to the CD47 promoter, increasing CD47 expression levels. CD47 is a critical molecule in "don't eat me" signaling. These data highlight the importance of the ERß-CD47 axis in the pathogenesis of endometriosis. We believe targeting CD47 may be a novel therapeutic approach for treating endometriosis and other ERß-associated diseases.

Human-Induced CD49a+ NK Cells Promote Fetal Growth.

CD49a+ natural killer (NK) cells play a critical role in promoting fetal development and maintaining immune tolerance at the maternal-fetal interface during the early stages of pregnancy. However, given their residency in human tissue, thorough studies and clinical applications are difficult to perform. It is still unclear as to how functional human CD49a+ NK cells can be induced to benefit pregnancy outcomes. In this study, we established three no-feeder cell induction systems to induce human CD49a+ NK cells from umbilical cord blood hematopoietic stem cells (HSCs), bone marrow HSCs, and peripheral blood NK cells in vitro. These induced NK cells (iNKs) from three cell induction systems display high levels of CD49a, CD9, CD39, CD151 expression, low levels of CD16 expression, and no obvious cytotoxic capability. They are phenotypically and functionally similar to decidual NK cells. Furthermore, these iNKs display a high expression of growth-promoting factors and proangiogenic factors and can promote fetal growth and improve uterine artery blood flow in a murine pregnancy model in vivo. This research demonstrates the ability of human-induced CD49a+ NK cells to promote fetal growth via three cell induction systems, which could eventually be used to treat patients experiencing adverse pregnancy outcomes.

Transcriptomic characteristics and impaired immune function of patients who retest positive for SARS-CoV-2 RNA.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has become a global public health crisis. Some patients who have recovered from COVID-19 subsequently test positive again for SARS-CoV-2 RNA after discharge from hospital. How such retest-positive (RTP) patients become infected again is not known. In this study, 30 RTP patients, 20 convalescent patients, and 20 healthy controls were enrolled for the analysis of immunological characteristics of their peripheral blood mononuclear cells. We found that absolute numbers of CD4+ T cells, CD8+ T cells, and natural killer cells were not substantially decreased in RTP patients, but the expression of activation markers on these cells was significantly reduced. The percentage of granzyme B-producing T cells was also lower in RTP patients than in convalescent patients. Through transcriptome sequencing, we demonstrated that high expression of inhibitor of differentiation 1 (ID1) and low expression of interferon-induced transmembrane protein 10 (IFITM10) were associated with insufficient activation of immune cells and the occurrence of RTP. These findings provide insight into the impaired immune function associated with COVID-19 and the pathogenesis of RTP, which may contribute to a better understanding of the mechanisms underlying RTP.

PBX1 expression in uterine natural killer cells drives fetal growth.

Abundant decidual natural killer (dNK) cells at the maternal-fetal interface are important during early pregnancy. However, functional subsets of dNK cells remain poorly understood. We describe a CD49a+PBX homeobox 1 (PBX1)+ dNK cell subset that promotes fetal development in humans and mice. The expression of PBX1 in dNK cells is up-regulated via the activated AKT1 pathway through the interaction of major histocompatibility complex G with the immunoglobulin-like transcript 2 receptor. PBX1 drives pleiotrophin and osteoglycin transcription in dNK cells, further promoting fetal development. Decreased PBX1 expression or the PBX1G21S mutant correlated with fetal growth restriction and pregnancy failure in patients with unexplained recurrent spontaneous abortion (URSA). Inactivation of Pbx1 in mouse dNK cells impairs fetal development by decreasing growth-promoting factors from CD49a+PBX1+ dNK cells. Impairment of PBX1 in dNK cells has positive correlation with URSA pathogenesis and may provide a potential marker for this condition.

PBX1 promotes development of natural killer cells by binding directly to the Nfil3 promoter.

The transcription factor nuclear factor interleukin-3-regulated protein (NFIL3, also called E4BP4) is crucial for commitment of natural killer (NK) cells from common lymphoid progenitors (CLPs). However, the identity of the factor that can regulate NFIL3 directly during the NK-cell development is not known. Here, we reveal that pre-B-cell leukemia transcription factor 1 (PBX1) can upregulate the NFIL3 expression directly. We used conditional knockout mice in which PBX1 in hematopoietic cells was specifically absent. The number of NK-committed progenitor pre-NKP cells and rNKP cells was reduced significantly in the absence of PBX1, which was consistent with NFIL3 deficiency. Also, the NFIL3 expression in NK cells was decreased if PBX1 was absent. We demonstrated that PBX1 was bound directly to the promoter of Nfil3 and facilitated transcription. Upon knockout of the binding site of PBX1 in the Nfil3 promoter, mice showed fewer NK-precursor cells and NK cells, just like that observed in Nfil3 knockout mice. Furthermore, asparagine N286 in the homeodomain of PBX1 controlled the binding of PBX1 to the Nfil3 promoter. Collectively, these findings demonstrate that the transcription factor PBX1 promotes the early development of NK cells by upregulating the Nfil3 expression directly.

QuEChERS pretreatment combined with high-performance liquid chromatography-tandem mass spectrometry for determination of aristolochic acids I and II in Chinese herbal patent medicines.

Aristolochic acid I and II (AA I and II), a kind of nephrotoxic and carcinogenic compound, are widely added in Chinese herbal patent medicines though they have been banned due to their toxicity. However, the traditional sample pre-treatment combined with the LC-MS analysis system is not effective to determine AAs in such complicated patent medicines. The QuEChERS pretreatment method possesses some merits such as being quick and effective. In this work, the modified QuEChERS method was first used to determine AA I and II in Chinese herbal patent medicines combined with the HPLC-MS/MS analysis system. Extraction and removal of target analytes from powder, tablet, and capsule samples were conducted using the modified QuEChERS pretreatment. The liquid extracts of Chinese herbal patent medicines could be analyzed directly. The method optimization results show that average recoveries ranged from 96.6% to 110.3% with relative standard deviations ranging from 4.2% to 13.0%. The quantization limits of the three selected matrices are estimated as follows (AA I/II): 2.8/6.5 ng mL-l in liquid herbal extract, 6.5/12.5 ng g-1 in tablets, and 22.1/42.1 ng g-1 in capsules. This method was conducted to investigate the presence of AAs, which are a type of nephrotoxic and carcinogenic carboxylic acid, in 30 herbal products sold through the Internet in China. AA I and II were detected in 53% and 20%, respectively, of tested samples.

Correction: QuEChERS pretreatment combined with high-performance liquid chromatography-tandem mass spectrometry for determination of aristolochic acids I and II in Chinese herbal patent medicines.

[This corrects the article DOI: 10.1039/D0RA03200J.].

Cytokine-Based Generation of CD49a+Eomes-/+ Natural Killer Cell Subsets.

Recent studies have identified CD49a+Eomes- and CD49a+Eomes+ subsets of tissue-resident NK (trNK) cells in different organs of the mouse. However, the characteristics of CD49a+Eomes-/+ NK cell development and the regulation of Eomes expression in NK cells remain unclear. Here, we established an in vitro cytokine-based feeder-free system in which bone marrow progenitor cells differentiate into CD49a+ NK cells. IL-15 was identified as being the key cytokine in this system that supported the development and maintenance of CD49a+ NK cells. The CD49a+ NK cells generated were Eomes-CD49b- and shared the same phenotype as hepatic trNK cells. IL-4 induced the expression of Eomes in generated NK cells and converted them into CD49a+Eomes+ cells, which were phenotypically and functionally similar to uterine trNK cells. Moreover, the IL-4/STAT6 axis was identified as being important in the generation of CD49a+Eomes+ induced NK cells. Collectively, these studies describe an approach to generate CD49a+Eomes-/+ subsets of NK cells and demonstrate important roles for IL-15 and IL-4 in the differentiation of these cells. These findings have potential for developmental research underlying the generation of different subsets of NK cells and the application of adoptive NK cell transfer therapies.

Utilization of primary care among college students with mental health disorders.

OBJECTIVE: Our goal was to assess whether integration of behavioral and medical services in college settings is associated with decreased use of primary care by patients with mental health diagnoses (MHDs). METHOD: The cohort consisted of 80,219 patients with at least 1 MHD in 21 universities. Two levels of service integration were defined: "standard"-universities with separate electronic health records (EHR) systems and minimal clinical collaboration between services, and "enhanced"-universities with shared EHR and collaborative patient care. Frequency, the total number of primary care visits, and complexity, the total visit length for primary care per unit time, were compared by using multilevel models. RESULTS: Nine schools met the criteria of enhanced clinical integration; a tenth school shifted to enhanced service during the study period. Student and patient demographics and clinical diagnoses were similar between the 2 categories. When controlling for variance in age, sex, and total time in school, patients with MHDs in standard systems had 15.72% (95% confidence interval [CI]: 10.77%-20.44%) more primary care visits and 22.88% (95% CI: 21.42%-24.38%) more time than patients in enhanced systems. CONCLUSIONS: Students with MHDs have significantly lower utilization of primary care services in integrated health care systems, but only a minority of institutions nationally have adopted this model of care. Although further research is needed to specifically assess differences in health outcomes and perceived suffering, it is possible that reduced primary care visits in enhanced integrative service settings with robust mental health support indicates overall reduction in perceived suffering for patients/clients. (PsycINFO Database Record

Planning Curvature-Constrained Paths to Multiple Goals Using Circle Sampling.

We present a new sampling-based method for planning optimal, collision-free, curvature-constrained paths for nonholonomic robots to visit multiple goals in any order. Rather than sampling configurations as in standard sampling-based planners, we construct a roadmap by sampling circles of constant curvature and then generating feasible transitions between the sampled circles. We provide a closed-form formula for connecting the sampled circles in 2D and generalize the approach to 3D workspaces. We then formulate the multi-goal planning problem as finding a minimum directed Steiner tree over the roadmap. Since optimally solving the multi-goal planning problem requires exponential time, we propose greedy heuristics to efficiently compute a path that visits multiple goals. We apply the planner in the context of medical needle steering where the needle tip must reach multiple goals in soft tissue, a common requirement for clinical procedures such as biopsies, drug delivery, and brachytherapy cancer treatment. We demonstrate that our multi-goal planner significantly decreases tissue that must be cut when compared to sequential execution of single-goal plans.